BackgroundThe accumulation of α-synuclein (α-syn), an essential step in PD development and progression, is observed not only in neurons but also in glia, including astrocytes. The mechanisms regulating astrocytic α-syn level and aggregation remain unclear. More recently, it has been demonstrated that a part of α-syn spreading occurs through extracellular vesicles (EVs), although it is unknown whether this process is involved in astrocytes of PD. It is known, however, that EVs derived from the central nervous system exist in the blood and are extensively explored as biomarkers for PD and other neurodegenerative disorders.MethodsPrimary astrocytes were transfected with A53T α-syn plasmid or exposed to α-syn aggregates. The level of astrocyte-derived EVs (AEVs) was assessed by nanoparticle tracking analysis and immunofluorescence. The lysosomal function was evaluated by Cathepsin assays, immunofluorescence for levels of Lamp1 and Lamp2, and LysoTracker Red staining. The Apogee assays were optimized to measure the GLT-1+ AEVs in clinical cohorts of 106 PD, 47 multiple system atrophy (MSA), and 103 healthy control (HC) to test the potential of plasma AEVs as a biomarker to differentiate PD from other forms of parkinsonism.ResultsThe number of AEVs significantly increased in primary astrocytes with α-syn deposition. The mechanism of increased AEVs was partially attributed to lysosomal dysfunction. The number of α-syn-carrying AEVs was significantly higher in patients with PD than in HC and MSA. The integrative model combining AEVs with total and aggregated α-syn exhibited efficient diagnostic power in differentiating PD from HC with an AUC of 0.915, and from MSA with an AUC of 0.877.ConclusionsPathological α-syn deposition could increase the astrocytic secretion of EVs, possibly through α-syn-induced lysosomal dysfunction. The α-syn-containing AEVs in the peripheral blood may be an effective biomarker for clinical diagnosis or differential diagnosis of PD.

BackgroundHip fracture creates a major burden on society due to high mortality, loss of independence and excess medical costs for older people. A multidisciplinary co-managed model of care is widely considered as the best practice for the management of older patients with hip fracture. The study aims to develop a conceptual framework to inform the future scale-up of this model of care through the identification of barriers and enablers that may influence successful uptake.MethodsThis qualitative study was conducted within an interventional study, which aimed to test the effectiveness of co-managed model of care for older patients with hip fracture. Health providers and health administrators from three hospitals were purposively selected and interviewed in-depth. The Consolidated Framework for Implementation Research (CFIR) was used to develop interview guides, collect and analyse data. Inductive and deductive approaches were used to generate enablers or barriers, aligned with the CFIR constructs. All barriers or enablers were inductively summarised to a conceptual framework with essential components to guide the implementation of co-managed model of care in other hospitals.ResultsA total of 13 health providers and 3 health administrators were recruited. The main barriers to co-managed care implementation included perceived complexity of implementation, insufficient international collaboration and incentives, the absence of national guideline support and lack of digital health applications for communication between health providers, insufficient number of health providers and beds, and poor understanding about the effectiveness of this care model. A conceptual framework for future scale-up was then developed, consisting of the following essential components: hospital authority support, enabling environment, adequate number of beds, sufficient and skilled health providers, use of digital health technology, regular quality supervision, evaluation and feedback, and external collaborations.ConclusionsDespite the complexity of the intervention, the co-managed model of care has the potential to be implemented and promoted in China and in similar settings, although there is a need to demonstrate feasibility in different settings.

ObjectiveTo investigate the epidemiological characteristics of syphilis cases detected among entry-exit personnel at Shanghai ports from 2014 to 2022 and the changing trend of the syphilis epidemic in the region so as to provide data support for the scientific and effective prevention and control of syphilis at ports.MethodsFrom January 2014 to December 2022, the subjects of syphilis screening at Shanghai port were selected. Physical examination and serological testing were used to confirm syphilis. All the data used were downloaded from the HIS system of Shanghai International Travel Healthcare Center. Descriptive epidemiology was used to analyze the characteristics of the detected cases, and the linear trend Chi-square test was used to analyze the trend between groups.ResultsFrom 2014 to 2022, a total of 918 cases of syphilis were detected among entry-exit personnel at Shanghai port, with a total detection rate of 154.68/100 000. The detection rate was the highest in 2015 and the lowest in 2022, showing a downward trend year by year since 2015. 54.36% of syphilis patients from East Asia were detected. Syphilis cases were reported in all age groups; most cases were under 39 years old, accounting for 36.06%. The syphilis detection rate in males was significantly higher than in females (79.63% vs. 20.4%). The main way of transmission was sexual transmission, accounting for 60.89%, among which male-to-male transmission was the primary way (22.36%).ConclusionThe detection rate of syphilis among entry-exit personnel at Shanghai port has been decreasing continuously in recent years. Targeted health intervention should be carried out according to the monitoring results.

BackgroundNeutrophils consume a large amount of energy when performing their functions. Compared with other white blood cells, neutrophils contain few mitochondria and mainly rely on glycolysis and gluconeogenesis to produce ATP. The inflammatory site is hypoxic and nutrient poor. Our aim is to study the role of abnormal adenosine metabolism of neutrophils in the asthmatic airway inflammation microenvironment.MethodIn this study, an asthma model was established by intratracheal instillation of Aspergillus fumigatus extract in Ecto-5'-Nucleotidase (CD73) gene–knockout and wild-type mice. Multiple analyses from bronchoalveolar lavage fluid (BALF) were used to determine the levels of cytokines and chemokines. Immunohistochemistry was used to detect subcutaneous fibrosis and inflammatory cell infiltration. Finally, adenosine 5’-(α, β-methylene) diphosphate (APCP), a CD73 inhibitor, was pumped subcutaneously before Aspergillus attack to observe the infiltration of inflammatory cells and subcutaneous fibrosis to clarify its therapeutic effect.ResultPAS staining showed that CD73 knockout inhibited pulmonary epithelial cell proliferation and bronchial fibrosis induced by Aspergillus extract. The genetic knockdownof CD73 significantly reduced the production of Th2 cytokines, interleukin (IL)-4, IL-6, IL-13, chemokine (C–C motif) ligand 5 (CCL5), eosinophil chemokine, neutrophil IL-17, and granulocyte colony-stimulating factor (G-CSF). In addition, exogenous adenosine supplementation increased airway inflammation. Finally, the CD73 inhibitor APCP was administered to reduce inflammation and subcutaneous fibrosis.ConclusionElevated adenosine metabolism plays an inflammatory role in asthma, and CD73 could be a potential therapeutic target for asthma.